Biomedical subjects

Ian Cunningham

Publications and source records attributed to Ian Cunningham.

3 recordsLinked to original sources

PubMed2024

Multi-omic Biomarkers Distinguish Rheumatoid Arthritis in Discordant Monozygotic Twins.

BACKGROUND: Although genetic factors have been identified in the pathogenesis of rheumatoid arthritis (RA), the concordance rate in monozygotic (MZ) twins is low, suggesting that other features contribute to disease development. Further, the relative contribution of such non-genetic elements in identical twins have not been characterized. Here, we aimed to measure differentiating host and microbial biomarkers of RA by studying MZ twins discordant for disease using a multi-omics approach. METHODS: Eight pairs of MZ twins discordant for RA (n=16) were enrolled. Gut microbiome was assessed using shotgun metagenomic sequencing. Autoantibodies, cytokines, and other plasma proteins were measured in both plasma and feces. Levels of short and medium-chain fatty acids from serum and feces were quantified using gas chromatography mass spectrometry (GC-MS). RESULTS: While overall microbiome diversity and composition did not significantly differ between twins, we observed a decrease in Blautia faecis in affected twins. Affected twins had higher concentrations of both fecal and plasma citrullinated and non-citrullinated autoantibodies, as well as significantly lower concentrations of fecal butyrate and propionate. CONCLUSION: Multi-omics biomarkers differentiate MZ twins discordant for RA. Blautia faecis, which is associated with reduced inflammatory cytokine expression, was decreased in RA twins. Similarly, short-chain fatty acids, known to have immune modulatory effects, were decreased in affected twins, suggesting further bi-directional interactions between inflammation at the gut barrier and disease state. If confirmed in other cohorts, exhaustive multi-omics approaches may improve our understanding of RA pathogenesis and potentially contribute to novel diagnostics and co-adjuvant therapies.

Journal Article↗

PubMed2005

Segmented crystalline scintillators: an initial investigation of high quantum efficiency detectors for megavoltage x-ray imaging.

Electronic portal imaging devices (EPIDs) based on indirect detection, active matrix flat panel imagers (AMFPIs) have become the technology of choice for geometric verification of patient localization and dose delivery in external beam radiotherapy. However, current AMFPI EPIDs, which are based on powdered-phosphor screens, make use of only approximately 2% of the incident radiation, thus severely limiting their imaging performance as quantified by the detective quantum efficiency (DQE) (approximately 1%, compared to approximately 75% for kilovoltage AMFPIs). With the rapidly increasing adoption of image-guided techniques in virtually every aspect of radiotherapy, there exist strong incentives to develop high-DQE megavoltage x-ray imagers, capable of providing soft-tissue contrast at very low doses in megavoltage tomographic and, potentially, projection imaging. In this work we present a systematic theoretical and preliminary empirical evaluation of a promising, high-quantum-efficiency, megavoltage x-ray detector design based on a two-dimensional matrix of thick, optically isolated, crystalline scintillator elements. The detector is coupled with an indirect detection-based active matrix array, with the center-to-center spacing of the crystalline elements chosen to match the pitch of the underlying array pixels. Such a design enables the utilization of a significantly larger fraction of the incident radiation (up to 80% for a 6 MV beam), through increases in the thickness of the crystalline elements, without loss of spatial resolution due to the spread of optical photons. Radiation damage studies were performed on test samples of two candidate scintillator materials, CsI(Tl) and BGO, under conditions relevant to radiotherapy imaging. A detailed Monte Carlo-based study was performed in order to examine the signal, spatial spreading, and noise properties of the absorbed energy for several segmented detector configurations. Parameters studied included scintillator material, septal wall material, detector thickness, and the thickness of the septal walls. The results of the Monte Carlo simulations were used to estimate the upper limits of the modulation transfer function, noise power spectrum and the DQE for a select number of configurations. An exploratory, small-area prototype segmented detector was fabricated by infusing crystalline CsI(Tl) in a 2 mm thick tungsten matrix, and the signal response was measured under radiotherapy imaging conditions. Results from the radiation damage studies showed that both CsI(Tl) and BGO exhibited less than approximately 15% reduction in light output after 2500 cGy equivalent dose. The prototype CsI(Tl) segmented detector exhibited high uniformity, but a lower-than-expected magnitude of signal response. Finally, results from Monte Carlo studies strongly indicate that high scintillator-fill-factor configurations, incorporating high-density scintillator and septal wall materials, could achieve up to 50 times higher DQE compared to current AMFPI EPIDs.

Computer Simulation↗

PubMed2002

Transanal endoscopic microsurgery: the first 50 cases.

BACKGROUND: Transanal endoscopic microsurgery is a form of minimally invasive rectal surgery first used at Cabrini Hospital in April 1997. This paper presents a prospective analysis of the first 50 cases with a median follow up of 33 months (range 20-48 months). METHODS: Prospective data was obtained from all cases between April 1997 and June 2000. RESULTS: Forty-nine patients (30 men and 19 women) underwent 50 procedures. Thirty-six had benign lesions and 14 malignant. The mean distance of the lower edge of the lesion from the anal verge was 8.7 cm. Three cases were converted to traditional transanal or transabdominal operations. Full-thickness excision was performed on 26 patients and the rectal wound was closed in 13 cases. The mean duration of transanal endoscopic microsurgery was 67 min (range 20-175), with a mean blood loss of 24 mL (0-300). The mean diameter and area of the fixed specimen was 3.7 cm (1.5-9.8) and 11.4 cm2 (0.8-18.9), respectively. Complications included postoperative fever (3), urinary retention (1) and per rectum bleeding (1). There was one death. The mean length of stay was 4 days. Histology confirmed complete excision in 39 (78%) cases and there have been two instances of local recurrence of adenoma (5%). CONCLUSIONS: Transanal endoscopic microsurgery is an effective, safe and cost-beneficial procedure for local excision of selected lesions in the middle and upper thirds of the rectum.

Aged↗